Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaerobically grown Escherichia coli contain an enzymatically active iron superoxide dismutase (Fe2-FeSOD) and an inactive iron-substituted manganese superoxide dismutase (Fe2-MnSOD). The anaerobic electron sink, nitrate plus paraquat, enhanced biosynthesis of the MnSOD polypeptide, with accumulation of inactive Fe2-MnSOD. The oxidant, diamide, in contrast, allowed anaerobic production of the active forms of MnSOD, i.e. Mn2-MnSOD and Mn/Fe-MnSOD. Nutritional supplementation with Mn(II) favored occupancy of the MnSOD active site with manganese and allowed anaerobic accumulation of Mn2-MnSOD in the absence of diamide. Enrichment of the anaerobic growth medium with Fe(II) both suppressed biosynthesis of the MnSOD polypeptide and inhibited formation of the active manganese-containing forms. A tac-sodA operon fusion was used to examine the effects of chelating agents and metals on maturation of nascent MnSOD, independent from the transcriptional effects these agents impose. Isopropyl-1-thio-beta-D-galactopyranoside (IPTG) elicited anaerobic biosynthesis of MnSOD, which accumulated as the inactive Fe2-MnSOD. Diamide, with IPTG, allowed formation of active Mn/Fe-MnSOD while 1,10-phenanthroline with IPTG resulted in accumulation of Mn2-MnSOD. These results suggest that iron participates in the redox-sensitive control of the formation of active MnSOD at two levels, i.e. that of transcription as well as that of maturation. During maturation of the nascent MnSOD polypeptide, iron and manganese compete for the metal-binding site; anaerobic conditions favor iron-binding, whereas oxidants, such as dioxygen or diamide, favor binding of manganese.
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PMID:Transcriptional and maturational effects of manganese and iron on the biosynthesis of manganese-superoxide dismutase in Escherichia coli. 157 50

Escherichia coli growing anaerobically respond to NO3- with a approximately 3-fold induction of active FeSOD and a approximately 5.5-fold induction of an inactive, but activatable form of MnSOD (pro-MnSOD). Paraquat, which mediates anaerobic electron flow to NO3-, increased the induction of pro-MnSOD to approximately 2.5-fold. Strains with defects in the SOD genes or which lacked nitrate reductase activity failed to accumulate active or pro-forms of SODs in response to NO3- +/- PQ++. Diamide caused anaerobic induction of active MnSOD and this effect was also observed in a glutathione-negative strain. These inductions required de novo synthesis of protein, even when cell content of pro-MnSOD had been elevated by exposure to NO3- +/- PQ++ prior to addition of diamide. These results indicate that oxidation of a cell component increases biosynthesis of the SOD gene product and this postulated oxidation can be caused by terminal electron acceptors, such as dioxygen or NO3-. In addition, it appears that insertion of the correct metal can be rate-limiting, leading to competition by other metals and to the accumulation of inactive, incorrectly substituted pro-forms. Metal insertion may be dependent upon the valence of the metal, which may be influenced, in turn, by the redox status of the cells. Diamide and redox active agents such as ferricyanide may thus allow anaerobic production of active MnSOD by favoring the production of a complexed form of Mn(III) which can compete favorably with other metal cations for the active site of nascent MnSOD.
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PMID:Anaerobic inductions of active forms of superoxide dismutases in Escherichia coli. 207 Oct 46

Transcriptional regulation of the sodA gene, a member of the soxRS regulon encoding the manganese-containing superoxide dismutase (MnSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) of Escherichia coli, was examined in a variety of regulatory mutants. Diamide, an oxidant that causes the anaerobic biosynthesis of the MnSOD polypeptide and also facilitates insertion of manganese at the active site, was found to anaerobically induce MnSOD in both soxRS and fur arcA fnr strains. Metal chelating agents also caused anaerobic induction of MnSOD in a fur arcA fnr triple mutant; however, this induction of MnSOD and of glucose-6-phosphate dehydrogenase (G6PD) by 1,10-phenanthroline was dependent on an intact soxRS locus. A strain of E. coli bearing a fusion of the soxS promoter to lacZ was used to demonstrate that both diamide and 1,10-phenanthroline caused anaerobic activation of soxS transcription. These results indicate that (i) both diamide and 1,10-phenanthroline induce the soxRS regulon anaerobically by stimulation of soxS transcription; (ii) diamide, but not metal chelators, also induces MnSOD biosynthesis by a soxRS-independent mechanism, perhaps mediated by effects on fur, arcA, or fnr-mediated repression of sodA; and (iii) the soxRS locus contains a metal-binding component and is responsive to the redox status of the cell.
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PMID:Induction of manganese-containing superoxide dismutase in anaerobic Escherichia coli by diamide and 1,10-phenanthroline: sites of transcriptional regulation. 846 Jan 39